The human fungal pathogen Cryptococcus neoformans is an opportunistic fungal pathogen and the causative agent of the disease cryptococcosis. Cryptococcus neoformans is able to rapidly and effectively adapt to varying conditions, favoring its survival in the environment and in the infected host. Infections caused by Cryptococcus neoformans and Cryptococcus gattii lead to more than 600,000 deaths per year (Park et al., 2009), especially among immunocompromised individuals. Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. In addition to afflicting the central nervous system, Cryptococcus neoformans can cause significant damage to most major organ systems including the heart, kidney and liver. Patients at particular risk are those with HIV/AIDS, autoimmune disorders, long term steroid treatments, and patients undergoing solid organ or bone marrow transplantation. Importantly, some species of Cryptococcus gattii have been shown to infect also immunocompetent subjects, causing mild to lethal pneumonia.
Many microbial phenotypes have been specifically correlated with virulence in these opportunistic pathogens, such as capsule production, melanin formation, and the secretion of various proteins. Additionally, cellular features such as the cell wall and morphogenesis play important roles in the interaction of Cryptococcus with host immune recognition and response pathways.
Despite its significant public health burden, no vaccines currently exist in the clinic for cryptococcosis (or other fungal infections Nanjappa and Klein, 2014). Although experimental vaccines have been developed using the glucuronoxylomannan (GXM) capsule bound to tetanus toxoid (Devi et al., 1991; Casadevall et al., 1992; Devi, 1996), these formulations have not been translated to the clinic and have suffered from drawbacks such as inducing detrimental antibodies in mice (Casadevall and Pirofski, 2005; Datta and Pirofski, 2006). Recent attempts in the mouse models of cryptococcosis have been focused on the use of genetically engineered C. neoformans strains that generate cytokines (Wormley et al., 2007; Wozniak et al., 2011) or protein preparations from C. gattii administered prior to infection (Chaturvedi et al., 2014). Although these attempts have provided valuable insights, studies are still limited and shortcomings exist. For example, complete immunity against C. gattii (responsible for severe infections in the USA; Datta et al., 2009; Walraven et al., 2011) has not been achieved (Chaturvedi et al., 2014) demonstrating the need for the development of more effective vaccines against fungal infections.